The Cancer Genetics Program consists of 12 Participating Members, representing total peer-reviewed funding of $5.1 Million in annual direct costs (7.3 Million in total costs). During the last two years, its Members generated a total of 106-cancer-relevant peer-reviewed publications, 7% of which were intra- and inter-programmatic collaborations. The Cancer Genetics Program is focused on using classical and molecular genetics in the study of cancer, both for understanding the mechanistic basis of the disease and for developing therapeutic interventions. The information coming onstream from Human Genome Project and the availability of tools for use in mutation detection, linkage analysis, positional cloning and candidate gene analysis have facilitated the gene discovery process. This is resulting in the continuing identification of genetic abnormalities involved in the development of various types of cancer. Additionally, the ready availability of experimental methods for the genetic modification of various types of cancer. Additionally, the ready availability of experimental methods for the genetic modification of both mouse and human cells have allowed investigators to study the significance and functional implications of these newly recognized abnormalities for the development and treatment of cancer directly in mammalian systems. Rapid progress in understanding model organisms like yeast, De. Melanogaster, X laevis and C. elegans, coupled with the realization that many molecular pathways that are important in the development of cancer in higher species and mammalian cells are conserved in model organisms, has led to the productive introduction of studies of such organisms into cancer research. Integrated application of these different but complementary approaches to mammalian genetics unify and accelerate our understanding of the interlocking disturbances in the structural and regulatory components of the genome which characterize the onset of neoplasia. To take advantage of these developments and bring them to bear on the cancer research program at UCSD, the Cancer Genetics Program has put emphasis on studying (1) Cancer-relevant Model Systems; (2) Mouse Cancer Genetics; (3) Mammalian Cancer Genetics and; (4) Clinical Cancer Genetics.